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  • HER2/ERBB2 overexpression in advanced gallbladder carcinoma: comprehensive evaluation by immunocytochemistry and fluorescence in situ hybridisation on fine-needle aspiration cytology samples

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HER2/ERBB2 overexpression in advanced gallbladder carcinoma: comprehensive evaluation by immunocytochemistry and fluorescence in situ hybridisation on fine-needle aspiration cytology samples
  1. Pragya Verma1,
  2. Parikshaa Gupta2,
  3. Nalini Gupta2,
  4. Radhika Srinivasan3,
  5. Pankaj Gupta4,
  6. Usha Dutta5,
  7. Shelly Sharma2,
  8. Radha Uppal2,
  9. Ritambhra Nada6,
  10. Anupam Lal4
  1. 1Department of Pathology, PGIMER, Chandigarh, India
  2. 2Department of Cytology and Gynecologic Pathology, PGIMER, Chandigarh, India
  3. 3Department of Cytology and Gynecologic Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
  4. 4Department of Radiodiagnosis, PGIMER, Chandigarh, India
  5. 5Department of Gastroenterology, PGIMER, Chandigarh, India
  6. 6Histopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
  1. Correspondence to Dr Parikshaa Gupta, Department of Cytology and Gynecologic Pathology, PGIMER, Chandigarh 160012, India; parikshaa{at}gmail.com

Abstract

Aims Advanced gallbladder carcinoma (AGBC) carries a poor prognosis with dismal survival. There are no data regarding HER2/ERBB2 expression in AGBC. This study evaluated the overexpression of HER2/ERBB2 in cytological aspirates from AGBCs to identify potential patients for whom anti-HER2 targeted therapies can benefit.

Methods This prospective, case–control study was performed on 50 primary AGBC cases. A detailed cytomorphological assessment, followed by immunocytochemistry (ICC) for HER2/ERBB2, was performed on AGBC cell blocks. A similar number of age-matched and gender-matched resected chronic cholecystitis specimens were included as controls. Fluorescence in situ hybridisation (FISH) was performed in equivocal cases.

Results A total of 10 (20%) cases showed positive (3+), 19 (38%) equivocal (2+) expression and 21 (42%) were negative on HER2/ERBB2 ICC. None of the equivocal cases demonstrated HER2 amplification by FISH. Among the controls, none showed positive (3+) immunoexpression, 23 (46%) demonstrated equivocal expression and 27 (54%) were negative. On statistical analysis, HER2/ERBB2 overexpression was significantly associated with AGBC compared with the controls. Of all the clinical, radiological and cytomorphological parameters, the predominant papillary or acinar arrangements of the tumour cells were significantly associated with HER2/ERBB2 overexpression.

Conclusions This is the first study to evaluate the expression of HER2/ERBB2 on cytological aspirates in AGBC using ICC and FISH. HER2/ERBB2 overexpression(20%) was significantly associated with AGBC. Furthermore, predominant papillary or acinar arrangements of tumour cells in the cytological smears were significantly associated with HER2/ERBB2 overexpression. They can serve as potential predictors of HER2/ERBB2 overexpression to select AGBC patients for anti-HER2 targeted therapies.

  • cancer
  • gallbladder neoplasms
  • immunohistochemistry
  • pathology, molecular
  • cytological techniques

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

https://doi.org/10.1136/jcp-2023-208940

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as online supplemental information.

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    Footnotes

    • Handling editor Runjan Chetty.

    • Twitter @drsradhika

    • Contributors PV: data collection, formal analysis, writing of the first draft, and approval of the final version of the manuscript. ParikshaaG: Guarantor, conceptualisation, data curation, data interpretation, formal analysis, methodology, supervision, validation, visualisation, writing—original draft and writing—review, editing, and approval of the final version of the manuscript. NG, RS and RN: data interpretation, formal analysis, supervision, visualisation, manuscript review and approval of the final version of the manuscript. PankajG, UD and AL: data collection, data interpretation, supervision, clinical patient management, manuscript review and approval of the final version of the manuscript. SS and RU: data collection, methodology, manuscript review and approval of the final version of the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.